Hello,
I'd like some advice regarding the exclusion criteria for a randomised clinical trial and how this should be represented on the screening CRF.

The study is a multi-centre international trial and the protocol has been approved in the majority of countries involved but when reviewed recently by the MHRA it was requested that an extra exclusion criteria be added excluding anyone with any known allergy to the study drugs or their components. I updated the protocol based on the MHRA’s requests as they were not happy for the trial to start in the UK until the protocol had been amended, and this has now been approved.

The trial is very close to starting in Spain (first patient scheduled to be randomised at the end of the month) and the CRFs and corresponding database have been finalised and do not incorporate this extra criteria in the screening checklist. The project manager for the trial does not want to delay the trial starting by submitting the protocol amendment in all the countries where the previous version has been accepted and has instructed that we only use the amended protocol in the UK but this is causing an issue with the extra exclusion criteria and how to deal with this on the CRFs. I am not entirely confident that starting a trial with two slightly protocols and different exclusion criteria is best practice.

I had suggested that the exclusion criteria be added to the CRF for all countries (and this is can be updated on the database reasonably easily) but the project manager does not feel it is appropriate to include this extra criteria for countries where this version of the protocol has not be been reviewed and approved.
Is it definitely necessary to add the extra exclusion criteria to the screening CRF?

Please can you advise on the best way forward with this matter and let me know the best practice for this scenario if possible.

Thanks for any help you can offer

21st Sep 2016, 12:32 PM

ajay_2686

Ajay

[FONT=arial]As per the Latest Updates from ICH Guideline E17 (step 2) [COLOR=#444444]general principles on planning/designing Multi-Regional Clinical Trial (MRCT).[/COLOR]
[/FONT]
2.2.2 Subject SelectionIn MRCTs, subject selection should be carefully considered to better understand andpossibly mitigate potential sources of regional variability and their impact on trialresults. Clear and specific inclusion and exclusion criteria that are acceptable and canbe applied across all regions should be included in the protocol.

So i think current regulatory thinking for this is that your suggestion is right.

[QUOTE=TM123;2773]Hello,
I'd like some advice regarding the exclusion criteria for a randomised clinical trial and how this should be represented on the screening CRF.

The study is a multi-centre international trial and the protocol has been approved in the majority of countries involved but when reviewed recently by the MHRA it was requested that an extra exclusion criteria be added excluding anyone with any known allergy to the study drugs or their components. I updated the protocol based on the MHRA’s requests as they were not happy for the trial to start in the UK until the protocol had been amended, and this has now been approved.

The trial is very close to starting in Spain (first patient scheduled to be randomised at the end of the month) and the CRFs and corresponding database have been finalised and do not incorporate this extra criteria in the screening checklist. The project manager for the trial does not want to delay the trial starting by submitting the protocol amendment in all the countries where the previous version has been accepted and has instructed that we only use the amended protocol in the UK but this is causing an issue with the extra exclusion criteria and how to deal with this on the CRFs. I am not entirely confident that starting a trial with two slightly protocols and different exclusion criteria is best practice.

I had suggested that the exclusion criteria be added to the CRF for all countries (and this is can be updated on the database reasonably easily) but the project manager does not feel it is appropriate to include this extra criteria for countries where this version of the protocol has not be been reviewed and approved.
Is it definitely necessary to add the extra exclusion criteria to the screening CRF?

Please can you advise on the best way forward with this matter and let me know the best practice for this scenario if possible.